ObjectiveTo investigate the effect and mechanism of Yishen Tongluo prescription in protecting mice from oxidative stress injury in diabetic kidney disease （DKD） via the nuclear factor erythroid 2-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1）/NAD（P）H quinone oxidoreductase 1 （NQO1） signaling pathway. MethodsSpecific pathogen-free （SPF） male C57BL/6 mice were assigned into a control group （n=10） and a modeling group （n=50）. The DKD model was established by intraperitoneal injection of streptozotocin. The mice in the modeling group were randomized into a model group， a semaglutide （40 μg·kg^-1） group， and high-， medium-， and low-dose （18.2， 9.1， 4.55 g·kg^-1， respectively） Yishen Tongluo prescription groups， with 10 mice in each group. The treatment lasted for 12 weeks. Blood glucose and 24-h urine protein levels were measured， and the kidney index （KI） was calculated. Serum levels of creatinine （SCr）， blood urea nitrogen （BUN）， alanine aminotransferase （ALT）， and aspartate aminotransferase （AST） were assessed. The pathological changes in the renal tissue were evaluated by hematoxylin-eosin， periodic acid-Schiff， periodic acid-silver methenamine， and Masson’s trichrome staining. Enzyme-linked immunosorbent assay kits were used to measure the levels of β2-microglobulin （β2-MG）， neutrophil gelatinase-associated lipocalin （NGAL）， kidney injury molecule-1 （KIM-1）， liver fatty acid-binding protein （L-FABP）， nitric oxide synthase （NOS）， glutathione （GSH）， total antioxidant capacity （T-AOC）， and 8-hydroxy-2'-deoxyguanosine （8-OHdG）. Immunohistochemical staining was performed to examine the expression of Kelch-like ECH-associated protein 1 （Keap1） and malondialdehyde （MDA）. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR） and Western blot were employed to determine the mRNA and protein levels， respectively， of factors in the Nrf2/HO-1/NQO1 signaling pathway. ResultsCompared with the control group， the DKD model group showed rises in blood glucose， 24-h urine protein， KI， SCr， BUN， and ALT levels， along with glomerular hypertrophy， renal tubular dilation， thickened basement membrane， mesangial expansion， and collagen deposition. Additionally， the model group showed elevated levels of β2-MG， NGAL， KIM-1， L-FABP， NOS， and 8-OHdG， lowered levels of GSH and T-AOC， up-regulated expression of MDA and Keap1， and down-regulated expression of Nrf2， HO-1， NQO1， and glutamate-cysteine ligase catalytic subunit （GCLC） （P<0.05）. Compared with the model group， the semaglutide group and the medium- and high-dose Yishen Tongluo prescription groups showed reductions in blood glucose， 24-h urine protein， KI， SCr， BUN， and ALT levels， along with alleviated pathological injuries in the renal tissue. In addition， the three groups showed lowered levels of β2-MG， NGAL， KIM-1， L-FABP， NOS， and 8-OHdG， elevated levels of GSH and T-AOC， down-regulated expression of MDA and Keap1， and up-regulated expression of Nrf2， HO-1， NQO1， and GCLC （P<0.05）. ConclusionYishen Tongluo prescription exerts renoprotective effects in the mouse model of DKD by modulating the Nrf2/HO-1/NQO1 signaling pathway， mitigating oxidative stress， and reducing renal tubular injuries.

Objective: To investigate the mechanism of Yishen Tongluo Formula in ameliorating renal pyroptosis in diabetic nephropathy mice by regulating the toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor-κB (NF-κB) signaling pathway. Methods: Sixty C57BL/6 male mice were randomly divided into control (10 mice) and intervention groups (50 mice) using random number table method. The diabetes nephropathy model was established by intraperitoneally injecting streptozotocin(50 mg/kg). After modeling, the intervention group was further divided into model, semaglutide (40 μg/kg), and high-, medium-, and low-dose Yishen Tongluo Formula groups (15.6, 7.8, and 3.9 g/kg, respectively) using random number table method. The high-, medium-, and low-dose Yishen Tongluo Formula groups were administered corresponding doses of medication by gavage, the semaglutide group received a subcutaneous injection of semaglutide injection, and the control group and model groups were administered distilled water by gavage for 12 consecutive weeks. Random blood glucose levels of mice in each group were monitored, and the 24-h urinary protein content was measured using biochemical method every 4 weeks; after treatment, the serum creatinine and urea nitrogen levels were measured using biochemical method. The weight of the kidneys was measured, and the renal index was calculated. Hematoxylin and eosin, periodic acid-Schiff, periodic Schiff-methenamine, and Masson staining were used to observe the pathological changes in renal tissue. An enzyme-linked immunosorbent assay was used to detect urinary β2-microglobulin (β2-MG), neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1) levels. Western blotting and real-time fluorescence PCR were used to detect the relative protein and mRNA expression levels of nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3), Caspase-1, gasdermin D (GSDMD), interleukin-1β (IL-1β), and interleukin-18 (IL-18) in renal tissue. Immunohistochemistry was used to detect the proportion of protein staining area of the TLR4, MyD88, and NF-κB in renal tissue. Results: Compared with the control group, the random blood glucose, 24-h urinary protein, serum creatinine, urea nitrogen, and renal index of the model group increased, and the urine β2-MG, NGAL, and KIM-1 levels increased. The relative protein and mRNA expression levels of NLRP3, Caspase-1, GSDMD, IL-1β, and IL-18 in renal tissue increased, and the proportion of TLR4, MyD88, and NF-κB protein positive staining areas increased (P<0.05). Pathological changes such as glomerular hypertrophy were observed in the renal tissue of the model group. Compared with the model group, the Yishen Tongluo Formula high-dose group showed a decrease in random blood glucose after 12 weeks of treatment (P<0.05). The Yishen Tongluo Formula high- and medium-dose groups showed a decrease in 24-h urinary protein, creatinine, urea nitrogen, and renal index, as well as decreased β2-MG, NGAL, and KIM-1 levels. NLRP3, Caspase-1, GSDMD, IL-1 β, and IL-18 relative protein and mRNA expression levels were also reduced, and the proportion of TLR4, MyD88, and NF-κB protein positive staining areas was reduced (P<0.05). Pathological damage to renal tissue was ameliorated. Conclusion Yishen Tongluo Formula may exert protective renal effects by inhibiting renal pyroptosis and alleviating tubular interstitial injury in diabetic nephropathy mice by regulating the TLR4/MyD88/NF-κB signaling pathway.

OBJECTIVE To investigate the ameliorative effects and potential mechanism of total secondary ginsenosides （TSG） on hypertrophic changes of primary cardiomyocytes stimulated by angiotensin Ⅱ （Ang Ⅱ）. METHODS Primary cardiomyocytes were isolated from the hearts of neonatal SD rats and divided into the following groups： control group， AngⅡ group （2 µmol/L）， TSG group （7.5 µg/mL）， PFK-015 group [6-phosphofructo-2-kinase/fructose-2， 6-bisphosphatase 3 （PFKFB3） inhibitor， 10 nmol/L]， and TSG+PFK-015 group （TSG 7.5 µg/mL+PFK-015 10 nmol/L）. The surface area， protein synthesis， energy metabolism-related indicators [free fatty acid （FFA）， coenzyme A （CoA）， acetyl coenzyme A （acetyl-CoA）]， and the expressions of glycolysis-related factors [hypoxia-inducible factor 1α （HIF-1α）， glucose transporter protein 4 （GLUT-4）， lactate dehydrogenase A （LDHA）， pyruvate dehydrogenase kinase 1 （PDK1） and PFKFB3] in primary cardiomyocytes of each group were measured. RESULTS Compared with the control group， the surface area of primary cardiomyocytes and protein synthesis were significantly increased， the content of FFA， protein and mRNA expressions of HIF-1α， LDHA， PDK1 and PFKFB3 were significantly increased or up-regulated in the AngⅡ group， while the contents of CoA and acetyl-CoA， the protein and mRNA expressions of GLUT-4 were significantly decreased or down-regulated （P＜0.05）. Compared with the AngⅡ group， both TSG group and PFK-015 group showed significant improvements in these indexes， with the TSG+PFK-015 group generally demonstrating superior effects compared to either treatment alone （P＜0.05）. CONCLUSIONS TSG can reduce the surface area of AngⅡ-induced primary cardiomyocytes， decrease protein synthesis， and inhibit their hypertrophic changes. These effects may be related to improving energy metabolism and the inhibition of glycolysis activity.

ObjectiveTo investigate the awareness and clinical practice of guidelines for the prevention and treatment of chronic hepatitis B （2022 edition） among clinicians. MethodsFrom July 19 to December 31， 2024， a self-designed electronic questionnaire was distributed via the WeChat mini program to collect related data from 1 588 clinicians nationwide， including their awareness and practice based on 18 questions regarding testing and referral， diagnosis and treatment， and follow-up. ResultsAmong all respondents， only 350 clinicians correctly understood all the updated key points of antiviral indications and treatment for special populations in the 2022 edition of guidelines for the prevention and treatment of chronic hepatitis B， with an overall awareness rate of 22.0%. Only 20% ‍—‍ ‍40% of the patients with positive HBV DNA and an age of >30 years receive antiviral therapy， while 80% ‍—‍ ‍100% of the patients with positive HBV DNA and a family history of hepatitis B cirrhosis or hepatocellular carcinoma receive antiviral therapy. The median follow-up rates at 1 year， 3 years， and 5 years were 67.5% 57.5% and 47.5%，respectively， showing a trend of gradual reduction， which might be associated with the influencing factors such as insufficient time for follow-up management by clinicians， insufficient awareness of the disease among patients， and poor adherence to follow-up. ConclusionThere is a gap between the awareness and practice of guidelines for the prevention and treatment of chronic hepatitis B （2022 edition） among clinicians. It is recommended to further strengthen training and focus on the whole process of “detection， diagnosis， treatment， and management” for patients with chronic hepatitis B in healthcare institutions， in order to promote the implementation of the guidelines.

Emergence agitation （EA） is a common complication after general anesthesia， especially in children and adolescents. Remifentanil， as a short-acting μ-receptor agonist， has become an important drug for the prevention and treatment of EA due to its rapid recovery and low risk of respiratory depression. This article reviews the mechanism of action and clinical research progress of remifentanil in the prevention and treatment of EA. Its mechanism of action involves the inhibition of pain signals mediated by traditional μ-receptor activation and potential new mechanism based on neural-endocrine-immune network， including regulation of microglial inflammatory pathways， and the modulation of cytokines and chemokines，etc. Clinical studies have shown that remifentanil can significantly shorten the recovery time， reduce the incidence of EA， and further optimize the analgesic effect and recovery quality by combining with other drugs （such as local anesthetics， sedatives， and opioid drugs）. Future research should further explore the mechanism of action of remifentanil， optimize clinical treatment strategies， and conduct large- scale clinical trials to standardize the drug use plan， while paying attention to its long-term effects and the development of multimodal treatment plans to promote the further development of EA prevention and treatment plans.

OBJECTIVE To optimize the water extraction technology for Kaixin granules. METHODS UPLC-MS/MS method was established for the simultaneous determination of ginsenoside Rg1， ginsenoside Re， ginsenoside Rb1， tenuifolin， polygalaxanthone Ⅲ and 3， 6′-disinapoyl-sucrose. An orthogonal test was designed with extraction times， extraction duration， and the volume of added water as factors. Using the contents of the aforementioned six indicator components and the extract yield as evaluation indexes， analytic hierarchy process-entropy weight method was employed to determine the combined weights of each indicator. Subsequently， process optimization and validation were conducted by integrating grey relational analysis （GRA） and back propagation （BP） neural network. RESULTS The water extraction technology optimized by the orthogonal test and GRA was 10- fold water for the first decoction and 8-fold water for the subsequent two， extracting 3 times，extracting for 1 h each time； the average comprehensive score of the validation experiment was 91.10 （RSD＝0.31%， n＝3）. The water extraction technology optimized by BP neural network was extracting 3 times with 10-fold water added each time， extracting for 1.5 h each time； the average comprehensive score of the validation experiment was 95.89 （RSD＝0.73%， n＝3）. Considering practical production requirements， the optimal water extraction technology was extraction performed three times， with 10-fold water for the first decoction and 8-fold water for the subsequent two extractions， with an extraction time of 1 h each. CONCLUSIONS The optimized water extraction technology for Kaixin granules is stable and feasible.

Objective: To construct and validate a prognosis model related to ferroptosis in urinary tract tumors using bioinformatics methods. Methods: RNA-seq and clinical data from TCGA′s BLCA and KIRC datasets were analyzed to establish the prognostic model, and then were validated using ICGC and GEO data. Prognostic genes associated with ferroptosis were identified through univariate Cox, LASSO-Cox, and multivariate Cox regression analyses. Co-expression and protein-protein interaction(PPI) network analyses determined the relationships among these genes. Immune infiltration analysis explored the association between ferroptosis-related prognostic genes and the immune microenvironment. Functional enrichment analysis of differentially expressed genes between high and low-risk groups in BLCA and KIRC prognostic models was conducted to investigate potential mechanisms by which ferroptosis-related genes regulate BLCA and KIRC prognosis. Results: Significant prognostic gene signatures associated with ferroptosis were identified in BLCA and KIRC. For BLCA, the genes EGR1, ZEB1, P4HB, WWTR1, JUN, CDO1,SCD,SREBF1,CAV1, and GALNT14 were significant. For KIRC, the genes ASMTL-AS1, CHAC1,MT1G, RRM2, TIMP1, DPEP1, GLRX5, and NDRG1 were significant. Ferroptosis-related miRNAs linked to the prognosis of both cancers were also identified. The constructed risk models based on these genes and miRNAs predicted patient prognosis in TCGA-BLCA and KIRC, with low-risk groups showing significantly higher overall survival(P<0.05). The hazard ratios for these models ranged from 2.54(95%CI: 1.73-3.74) to 4.74(95%CI: 3.47-6.47), with AUC values above 0.60. Co-expression analysis and PPI networks revealed high correlation levels between JUN and EGR1 in BLAC and between SCD and SREBF1. Immune infiltration analysis indicated positive correlations between EGR1, CAV1, JUN, and immune scores, while SREBF1 showed a negative correlation. Conclusion The prognosis model based on ferroptosis-related genes effectively predicts patient outcomes in BLCA and KIRC. This model can serve as a reference for targeting ferroptosis to assess the prognosis of BLCA and KIRC patients.

This paper systematically analyzed the ancient monographs of acupuncture and moxibustion and comprehensive medical books from pre-Qin to 1911， and extracted the data according to the etiology and pathogenesis， treatment principles and methods， acupoint selection， needling and moxibustion， and taboos of needling and moxibustion. The pathogenesis of migraine in ancient books and documents is summarized as "the causes are diverse， and phlegm-dampness is the majority". For treatment， the features include "needling has a sequence， and the root and the branch should be treated separately" and "focusing on tonifying deficiency and drain excess". It is also obtained of the rich ideas of acupoints selection， extensive application records of moxibustion， unique application of bloodletting therapy and clear explanation of acupuncture and moxibustion taboos. All mentioned above is expected to enrich the ideas and methods of modern migraine treatment and improve the clinical effects.

Objective:To investigate the effectiveness and feasibility of a 3D U-Net in conjunction with a three-phase CT image segmentation model in the automatic segmentation of GTVnx and GTVnd in nasopharyngeal carcinoma.Methods:A total of 645 sets of computed tomography (CT) images were retrospectively collected from 215 nasopharyngeal carcinoma cases, including three phases: plain scan (CT), contrast-enhanced CT (CTC), and delayed CT (CTD). The dataset was grouped into a training set consisting of 172 cases and a test set comprising 43 cases using the random number table method. Meanwhile, six experimental groups, A1, A2, A3, A4, B1, and B2, were established. Among them, the former four groups used only CT, only CTC, only CTD, and all three phases, respectively. The B1 and B2 groups used phase fine-tuning CTC models. The Dice similarity coefficient (DSC) and 95% Hausdorff distance (HD95) served as quantitative evaluation indicators.Results:Compared to only monophasic CT (group A1/A2/A3), triphasic CT (group A4) yielded better result in the automatic segmentation of GTVnd (DSC: 0.67 vs. 0.61, 0.64, 0.64; t = 7.48, 3.27, 4.84, P < 0.01; HD95: 36.45 vs. 79.23, 59.55, 65.17; t = 5.24, 2.99, 3.89, P < 0.01), with statistically significant differences ( P < 0.01). However, triphasic CT (group A4) showed no significant enhancement in the automatic segmentation of GTVnx compared to monophasic CT (group A1/A2/A3) (DSC: 0.73 vs. 0.74, 0.74, 0.73; HD95: 14.17 mm vs. 8.06, 8.11, 8.10 mm), with no statistically significant difference ( P > 0.05). For the automatic segmentation of GTVnd, group B1/B2 showed higher automatic segmentation accuracy compared to group A1 (DSC: 0.63, 0.63 vs. 0.61, t = 4.10, 3.03, P<0.01; HD95: 58.11, 50.31 mm vs. 79.23 mm, t = 2.75, 3.10, P < 0.01). Conclusions:Triphasic CT scanning can improve the automatic segmentation of the GTVnd in nasopharyngeal carcinoma. Additionally, phase fine-tuning models can enhance the automatic segmentation accuracy of the GTVnd on plain CT images.

Objective To analyze the evaluation value of serum troponin Ⅰ(TnⅠ)combined with soluble CD163(sCD163)in the disease condition and prognosis of the patients with acute cholecystitis.Methods The clinical data of 125 patients with acute cholecystitis admitted and treated in the hospital from October 2022 to October 2023 were retrospectively collected.The patients were divided into the mild group(n=33),moderate group(n=51)and severe group(n=41)according to the severity of disease condition.The levels of serum TnⅠ,sCD163,interleukin(IL)-6,C reactive protein(CRP),total bilirubin(TBIL)and alanine aminotrans-ferase(ALT)were detected.The patients were divided into the good prognosis group(n=95)and poor prog-nosis group(n=30)according the occurrence of complications such as abdominal pain,dyspepsia and cholan-gitis within postoperative 3 months.The preoperative indicators were compared between the two groups.The influencing factors of prognosis in the patients were evaluated by the logistic regress analysis.The receiver op-erating characteristic(ROC)curve was used to analyze the diagnostic efficiency of TnⅠ and sCD163 in evalua-ting the disease condition and prognosis of the patients.Results The levels of TnⅠ,sCD163,IL-6,CRP,TBIL and ALT in the mild group were(0.78±0.23)μg/L,(25.01±3.15)mg/L,(62.52±7.61)pg/mL,(32.47±4.11)mg/L,(35.65±4.61)μmol/L and(79.75±7.23)U/L respectively,which were lower than those in the moderate group and severe group(P＜0.05).The TnⅠ level in the good prognosis group was(0.99±0.37)μg/L,which was lower than(1.82±0.51)μg/L in the poor prognosis group(P＜0.05);the sCD163 level in the good prognosis group was(27.46±3.50)mg/L,which was lower than[(33.12±4.13)mg/L]in the poor prognosis group(P＜0.05).The logistic analysis showed that TnⅠ,SCD163,IL-6,CRP,TBIL and ALT all were the important factors affecting the prognosis in the patients;the ROC curve showed the area under the curve(AUC)of TnⅠ combined with SCD163 for evaluating the disease condition was 0.966(95％CI:0.937-0.995),which for evaluating the prognosis was 0.948(95％CI:0.903-0.993).Conclusion Serum TnⅠ com-bined with sCD163 has a high application value in the assessment of the disease condition and prognosis in the patients with acute cholecystitis.